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Sponsors and Collaborators: |
Leo W. Jenkins Cancer Center Genentech |
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Information provided by: | Leo W. Jenkins Cancer Center |
ClinicalTrials.gov Identifier: | NCT00600210 |
This trial is designed to study the safety and efficacy of the combination of carboplatin, bevacizumab, and pelvic radiation therapy.
Rationale for substituting cisplatin with carboplatin:
Five landmark trials in cervical cancer prompted the National Cancer Institute in February of 1999 to issue a clinical announcement stating that "strong consideration should be given to adding concurrent chemotherapy in the treatment of invasive cervical cancer". The chemotherapeutic agent which was a common denominator to all 5 trials was cisplatin, and ever since it has become part of the standard of care for the treatment of stage IIB, III, and IVA cervical cancers. In addition, chemoradiotherapy with cisplatin is also considered one of the standard treatment options for IB2 and IIA tumors greater than 4 cm in diameter.
The most recent Gynecologic Oncology Group protocols for cervical cancer have used cisplatin and radiation therapy as in two of the five landmark trials.
However, the benefit in survival given by cisplatin has not been without toxicity. In summary, in the trial by Keys 35% of patients receiving cisplatin and radiotherapy experienced moderate or severe toxicities. In the one by Rose, only 49 % completed the intended 6 cycles of chemotherapy.
Based on the toxicity profile of cisplatin, Higgins performed a phase II study of concurrent carboplatin with pelvic radiation therapy in the primary treatment of cervix cancer. He demonstrated the ability to administer carboplatin with concurrent radiation therapy with significantly less toxicity and with 94 % of the planned treatments delivered. A comprehensive analysis of the literature from 1998 which compared the efficacy of carboplatin versus cisplatin in solid tumors concluded that for ovarian cancer and lung cancer the effectiveness of carboplatin was comparable to cisplatin, while for germ cell tumors, bladder cancer, and head and neck cancer cisplatin appeared superior. There was no mention of cervical cancer in this review, since at present there is no phase III trial comparing carboplatin versus cisplatin in cervix cancer.
Rationale for bevacizumab:
Bevacizumab is a recombinant humanized monoclonal IgG1 antibody that binds to and inhibits the biologic activity of vascular endothelial growth factor (VEGF) which stimulates tumor and tumor blood vessel growth. Targeting VEGF with bevacizumab could potentially be of benefit in cervical cancer patients by starving the tumor's blood supply and potentially enhancing the effect of radiotherapy and carboplatin chemotherapy.
Condition | Intervention | Phase |
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Cervical Cancer |
Drug: Bevacizumab Drug: Carboplatin Radiation: Radiation Therapy |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Single Group Assignment |
Official Title: | AVF3963s Neoadjuvant Bevacizumab and Carboplatin Followed by Concurrent Bevacizumab, Carboplatin and Radiotherapy in the Primary Treatment of Cervix Cancer |
Estimated Enrollment: | 30 |
Study Start Date: | January 2008 |
Estimated Primary Completion Date: | January 2010 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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I: Experimental |
Drug: Bevacizumab
Bevacizumab will be delivered intravenously on day -7 at a dose of 10 mg/kg followed by carboplatin AUC 2.0 intravenously. This will allow therapy to start one week before starting radiotherapy to assess the initial tolerability of the combination without having radiation as a confounding factor, to start treatment while the patient's radiation is being planned, and to possibly optimize the tumor vasculature and allow optimal carboplatin delivery by the time chemoradiotherapy starts. Thereafter, bevacizumab will be given intravenously at 10 mg/kg every two weeks. Carboplatin will be given intravenously weekly at AUC 2.0. On weeks where both drugs are given, bevacizumab will be given first since it could help sensitize the tumor cells to carboplatin.
Drug: Carboplatin
Bevacizumab will be delivered intravenously on day -7 at a dose of 10 mg/kg followed by carboplatin AUC 2.0 intravenously. This will allow therapy to start one week before starting radiotherapy to assess the initial tolerability of the combination without having radiation as a confounding factor, to start treatment while the patient's radiation is being planned, and to possibly optimize the tumor vasculature and allow optimal carboplatin delivery by the time chemoradiotherapy starts. Thereafter, bevacizumab will be given intravenously at 10 mg/kg every two weeks. Carboplatin will be given intravenously weekly at AUC 2.0. On weeks where both drugs are given, bevacizumab will be given first since it could help sensitize the tumor cells to carboplatin.
Radiation: Radiation Therapy
Whole pelvis will be treated to a total dose of 45 Gy in 5 weeks. Cesium will be used with standard intracavitary systems preferably in two intracavitary applications. An effort should be made to deliver a minimum cumulative external and intracavitary dose to Point A of 85 Gy in 2 insertions. |
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Hiram Gay, MD | 252-744-2900 | gayh@ecu.edu |
Contact: Mindy Friday, RN | 252-744-1015 | fridaym@ecu.edu |
United States, North Carolina | |
East Carolina University School of Medicine | Recruiting |
Greenville, North Carolina, United States, 27834 | |
Contact: Hiram Gay, MD 252-744-2900 gayh@ecu.edu | |
Contact: Mindy Friday, RN 252-744-1015 fridaym@ecu.edu |
Principal Investigator: | Hiram Gay, MD | East Carolina University School of Medicine |
Responsible Party: | East Carolina Unvirsity School of Medicine ( Hiram Gay, MD, Principal Investigator ) |
Study ID Numbers: | AVF3963s |
Study First Received: | January 11, 2008 |
Last Updated: | February 20, 2009 |
ClinicalTrials.gov Identifier: | NCT00600210 History of Changes |
Health Authority: | United States: Food and Drug Administration |
Genital Diseases, Female Uterine Cervical Neoplasms Uterine Cervical Diseases Genital Neoplasms, Female Uterine Diseases |
Uterine Neoplasms Urogenital Neoplasms Carboplatin Bevacizumab Angiogenesis Inhibitors |
Antineoplastic Agents Growth Substances Physiological Effects of Drugs Genital Neoplasms, Female Uterine Diseases Urogenital Neoplasms Bevacizumab Carboplatin Angiogenesis Inhibitors Pharmacologic Actions |
Uterine Cervical Neoplasms Genital Diseases, Female Neoplasms Uterine Cervical Diseases Neoplasms by Site Therapeutic Uses Uterine Neoplasms Growth Inhibitors Angiogenesis Modulating Agents |